Molecular Motion and Heteronuclear Relaxation Part I – Lecture Outline
Chris Brosey, 11/16/2010
Overview
Why study biomolecular dynamics?
Brief survey of protein motion:
Global rotational diffusion – the diffusion tensor
Local NH bond fluctuations – the model-free formalism, extended model-free formalism
Bringing all motions together – the spectral density function
Finding a way to study motion with NMR – how motion stimulates relaxation of
excited nuclei
How can we measure protein motion by monitoring NMR relaxation?
Expressions for relaxation rates in terms of spectral density values at transition
frequencies, J(w)
Molecular Motion and Heteronuclear Relaxation Part II – Lecture Outline
Chris Brosey, 11/18/2010
Measuring relaxation rates – R1, R2, and NOE pulse sequences and data analysis
Spectral density mapping
Full versus reduced approaches
Analysis of Motion
Diffusion tensor extraction
Model-Free analysis
Brief overview of different schools of thought – ModelFree (Palmer), relax (d’Auvergne)
Examples from our lab and the literature
Up and coming areas for biomolecular dynamics and NMR relaxation
Molecular Motion and Heteronuclear Relaxation
References and Further Reading
Reviews
Korzhnev, D.M., Billeter, M., Arseniev, A.S., and Orekhov, V.Y. NMR studies of Brownian
tumbling and internal motions in proteins. Proj. Nuc. Mag. Res. Spec., 38: 197-266 (2001).
Palmer, A.G. NMR probes of molecular dynamics: Overview and comparison with other
techniques. Annu. Rev. Biophys. Biomol., 30: 129-55 (2001).
Luginbuhl, P. and Wuthrich, K. Semi-classical nuclear spin relaxation theory revisited for use
with biological macromolecules. Proj. Nuc. Mag. Res. Spec., 40: 199-247 (2002).
Palmer, A. NMR characterization of the dynamics of biomacromolecules. Chem. Rev., 104:
3623-3640 (2004).
Morin, S. A practical guide to protein dynamics from 15N spin relaxation in solution. Prog. NMR
Spec. (in press).
Kleckner, I.R. and Foster, M.P. An introduction to NMR-based approaches for measuring
protein dynamics. BBA - Proteins and Proteomics (in press).
Boehr, D.D., Dyson, H.J., and Wright, P.E. An NMR perspective on enzyme dynamics. Chem.
Rev. 106: 3055-79 (2006).
Diffusion tensor calculations
Bruschweiler, R., Liao, X., Wright, P.E. Long-range motional restrictions in a multidomain zincfinger protein from anisotropic tumbling. Science, 268: 886-80 (1995).
Tjandra, N., Feller, S.E., Pastor, R.W., and Bax, A. Rotational diffusion anisotropy of human
ubiquitin from 15N NMR relaxation. JACS, 117: 12562-66 (1995).
Fushman, D., Xin, R., and Cowburn, D. Direct determination of changes of interdomain
orientation on ligation: Use of the orientational dependence of 15N NMR relaxation in Abl
SH(32). Biochemistry, 38: 10225-30 (1999).
Walker, O., Varadan, R., and Fushman, D. Efficient and accurate determination of the overall
rotational diffusion tensor of a molecule from 15N relaxation data using computer program
ROTDIF. J. Mag. Res., 168: 336-45 (2004).
Model-free formalism (MF) and Extended model-free formalism (EMF)
Lipari, G. and Szabo, A. Model-free approach to the interpretation of nuclear magnetic
resonance relaxation in macromolecules. I. Theory and range of validity. JACS, 104: 4546-59
(1982).
Lipari, G. and Szabo, A. Model-free approach to the interpretation of nuclear magnetic
resonance relaxation in macromolecules. II. Analysis of experimental results. JACS, 104: 455970 (1982).
Clore, G.M., Szabo, A., Bax, A., Kay, L.E., Driscoll, P.C., Gronenborn, A.M. Deviations from the
simple two-parameter model-free approach to the interpretation of nitrogen-15 nuclear magnetic
relaxation of proteins. JACS, 112: 4989-91 (1990).
Classic examples of heteronuclear relaxation studies and model-free analysis
Palmer, A.G., Rance, M., and Wright, P.E. Intramolecular motions of a zinc finger DNA-binding
domain from xfin characterized by proton-detected natural abundance 13C heteronuclear NMR
spectroscopy. JACS, 113: 4371-80 (1991).
Mandel A.M., Akke, M., Palmer, A.G. Backbone dynamics of Escherichia coli ribonuclease HI:
correlations with structure and function in an active enzyme. J. Mol. Biol., 246: 144-63 (1995).
Hydrodynamic R1 and R2 prediction software
De la Torre, J.G., Huertas, M.L., and Carrasco, B. HYDRONMR: Prediction of NMR relaxation
of globular proteins from atomic-level structures and hydrodynamic calculations. J. Mag. Res.,
147: 138-46 (2000).